PT  - JOURNAL ARTICLE
AU  - Frederick A. Partridge
AU  - Anwen E. Brown
AU  - Steven D. Buckingham
AU  - Nicky J. Willis
AU  - Graham M. Wynne
AU  - Ruth Forman
AU  - Kathryn J. Else
AU  - Alison A. Morrison
AU  - Jacqueline B. Matthews
AU  - Angela J. Russell
AU  - David A. Lomas
AU  - David B. Sattelle
TI  - An automated high-throughput system for phenotypic screening of chemical libraries on <em>C. elegans</em> and parasitic nematodes
AID  - 10.1101/187427
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 187427
4099  - http://biorxiv.org/content/early/2017/09/11/187427.short
4100  - http://biorxiv.org/content/early/2017/09/11/187427.full
AB  - Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known anthelmintics against model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified known anthelmintics, including tolfenpyrad, auranofin, and mebendazole and 14 compounds previously undescribed as anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel anthelmintics.